: Despite significant advances in the treatment of HIV infection, there are a number of unresolved issues in AIDS chemotherapy, including viral resistance, viral reservoir, salvage therapy and potential elimination of the virus. In order to solve all these problems, the critical need in the future will be the discovery of more potent and selective new anti-HIV regimens with different patterns of resistance than approved drugs. This proposal is a continuation of ongoing drug discovery efforts in the area of antiviral nucleosides at the University of Georgia and the Emory University/VA Medical Center. The investigators propose to explore the chemistry and virology of the following classes of mainly L-nucleosides: (1) oxaselenolane nucleosides; (2) fluorinated L-D4N; (3) 2-substituted L-carbocyclic nucleosides; (4) L-apionucleosides; (5) L-oxetanocin analogs; (6) cyclobutane carbocyclic L-nucleosides; (7) conformationally restricted endo-cyclopropropylnucleosides; (8) homo- cyclopropylcarbocyclic nucleosides.